高三尖杉酯碱对白血病细胞凋亡、增殖的影响及对Ras/Raf/MEK通路的抑制作用

doi:10.20047/j.issn1673-7210.2023.25.03

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Abstract Objective To investigate the effect of homoharringtonine (HHT) on apoptosis and proliferation of leukemia cells and its inhibitory effect on Ras/Raf/MEK pathway. Methods The logarithmic growth phase K562 and Kasum-1 cells were taken for study and treated with HHT of 0, 10, 20 , and 50 ng/ml, respectively. MTT was used to detect relative cell viability, clone formation assay was used to detect the number of cell clones, cell IC50 was calculated at 24, 48, and 72 hours, flow cytometry was used to detect the level of apoptosis, and Western blot was used to detect the relative levels of Ras/Raf/MEK pathway proteins and apoptosis-related proteins. Results At 24, 48, and 72 hours, the IC50 of HHT on K562 cells was 80.69, 65.28, and 50.76 ng/ml, respectively. The IC50 of HHT on Kasum-1 cells was 85.16, 70.11, and 51.14 ng/ml, respectively. When cultured for 24, 48, and 72 h, the survival rate of 10, 20 and 50 ng/ml HHT cells was lower than 0 ng/ml, and the survival rate of 20 and 50 ng/ml HHT cells was lower than 10 ng/ml. The survival rate of 50 ng/ml HHT cells was lower than that of 20 ng/ml HHT cells, and the differences were statistically significant (P＜0.05). The clones of 10, 20 and 50 ng/ml HHT cells were all lower than 0 ng/ml; the clones of 20 and 50 ng/ml HHT cells were all lower than 10 ng/ml HHT cells; the clones of 50 ng/ml HHT cells were all lower than 20 ng/ml HHT cells, and the differences were statistically significant (P＜0.05). The apoptosis rate of 10, 20, and 50 ng/ml HHT cells was higher than that of 0 ng/ml HHT cells, the apoptosis rate of 20 and 50 ng/ml HHT cells was higher than that of 10 ng/ml HHT cells, and the apoptosis rate of 50 ng/ml HHT cells was higher than that of 20 ng/ml HHT cells, and the differences were statistically significant (P＜0.05). The expression levels of RAS, p-cRAF, and p-MEK protein at 10, 20, and 50 ng/ml HHT were all lower than 0 ng/ml HHT, and the expression levels of RAS, p-cRAF, and p-MEK protein at 20 and 50 ng/ml HHT were all lower than 10 ng/ml HHT. The expression levels of RAS, p-cRAF, and P-MEK at 50 ng/ml HHT were lower than those of 20 ng/ml HHT, and the differences were statistically significant (P＜0.05). Survivan expression levels at 10, 20, and 50 ng/ml HHT were lower than 0 ng/ml HHT, Cleaved caspase-3 and Cleaved PARP were higher than 0 ng/ml HHT. Survivan expression at 20 and 50 ng/ml HHT was lower than that at 10 ng/ml HHT. Survivan expression levels were lower than 10, and 50 ng/ml HHT, respectively, Cleaved caspase-3 and Cleaved PARP expression levels were higher than 20 ng/ml HHT. The protein expression levels of Cleaved caspase-3 and Cleaved PARP were higher than 20 ng/ml HHT, and the differences were statistically significant (P＜0.05). Conclusion HHT can inhibit the activity of Ras/Raf/MEK pathway, inhibit the proliferation of leukemia cells, and promote apoptosis of leukemia cells.

Key words： Homoharringtonine Ras/Raf/MEK pathway Leukemia Apoptosis Proliferation

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	QI Haiyan LAN Jianping SONG Xiaolu WANG Xiaogang WANG Wensong

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QI Haiyan LAN Jianping SONG Xiaolu WANG Xiaogang WANG Wensong. Effect of homoharringtonine on lapoptosis and proliferation of leukemia cells and its inhibitory effect on Ras/Raf/MEK pathway[J]. 中国医药导报, 2023, 20(25): 20-25,42.

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https://www.yiyaodaobao.com.cn/EN/10.20047/j.issn1673-7210.2023.25.03 OR https://www.yiyaodaobao.com.cn/EN/Y2023/V20/I25/20

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